RT Journal Article
T1 Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2.
A1 Yeste, Ada
A1 Takenaka, Maisa C
A1 Mascanfroni, Ivan D
A1 Nadeau, Meghan
A1 Kenison, Jessica E
A1 Patel, Bonny
A1 Tukpah, Ann-Marcia
A1 Babon, Jenny Aurielle B
A1 DeNicola, Megan
A1 Kent, Sally C
A1 Pozo, David
A1 Quintana, Francisco J
AB Type 1 diabetes (T1D) is a T cell-dependent autoimmune disease that is characterized by the destruction of insulin-producing β cells in the pancreas. The administration to patients of ex vivo-differentiated FoxP3(+) regulatory T (Treg) cells or tolerogenic dendritic cells (DCs) that promote Treg cell differentiation is considered a potential therapy for T1D; however, cell-based therapies cannot be easily translated into clinical practice. We engineered nanoparticles (NPs) to deliver both a tolerogenic molecule, the aryl hydrocarbon receptor (AhR) ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), and the β cell antigen proinsulin (NPITE+Ins) to induce a tolerogenic phenotype in DCs and promote Treg cell generation in vivo. NPITE+Ins administration to 8-week-old nonobese diabetic mice suppressed autoimmune diabetes. NPITE+Ins induced a tolerogenic phenotype in DCs, which was characterized by a decreased ability to activate inflammatory effector T cells and was concomitant with the increased differentiation of FoxP3(+) Treg cells. The induction of a tolerogenic phenotype in DCs by NPs was mediated by the AhR-dependent induction of Socs2, which resulted in inhibition of nuclear factor κB activation and proinflammatory cytokine production (properties of tolerogenic DCs). Together, these data suggest that NPs constitute a potential tool to reestablish tolerance in T1D and potentially other autoimmune disorders.
YR 2016
FD 2016-06-21
LK http://hdl.handle.net/10668/10203
UL http://hdl.handle.net/10668/10203
LA en
DS RISalud
RD Apr 11, 2025